In 2013, it was noted in Blum 2013, Chapter 2, Section, 2.5, p. 39:                When almost half-of the US population have indulged in illegal drug practices, when our presidential candidates are forced to dodge the tricky question of their past history involving illegal drug use, and when almost every American has sloshed down a martini or two in their life time, there must be a reason, there must be a need, there must be a natural response for humans to imbibe at such high rates. There is even a more compelling question surrounds the millions who seek out high risk novelty. Why do millions have this innate drive in face of putting themselves in Harm's way? Why are millions paying the price of their indiscretions in our jails, in hospitals, in wheel chairs and are lying dead in our cemeteries. What price must we pay for pleasure seeking or just plain getting “HIGH”? Maybe the answer lies within our brain. Maybe it is in our genome?        
Reward Deficiency Syndrome (RDS) was first defined by the inventor and his lab in 1996 as a putative predictor of impulsive and addictive behaviors. [Blum 2000; Blum 1996; Comings 2000]. See also TABLE 1.
TABLE 1The Reward Deficiency Syndrome Behaviors (RDS).ADDITIVE BEHAVIORSIMPULSE BEHAVIORSOBESSIVESubstanceNon SubstanceSpectrumDisruptiveCOMPULSIVEPERSONALITYRelatedRelatedDisordersImpulsiveBEHAVIORSDISORDERSAlcoholThrill seekingAttention-Anti-socialBodyParanoid(novelty)deficitDysmorphicHyperactivityCannabisSexualTourette andConductHoardingSchizoidSadismTic SyndromeOpioidsSexualAutismIntermittentTrichotillo-BorderlineMasochismExplosivemania (hairpulling)Sedatives/HypersexualOppositionalExcoriationSchizotypalHypnoticsDefiant(skin picking)StimulantsGamblingExhibitionisticNon-suicidalHistrionicSelf-InjuryTobaccoInternetNarcissisticGamingGlucoseAvoidantFoodDependent
The molecule dopamine after binding to the dopamine D2 receptor has been associated with many behaviors (Dackis and Gold 1985; Di Chiara and Imperato 1988) and the DRD2 has been referred to as a reward gene [Blum et al 1990; Eisenberg 2007; Hietala I 1994; Hietala II 1994; Volkow 2001; Volkow 2002]. Although the DRD2 gene and especially the TaqI A1 allele have been most associated with neuropsychiatric disorders in general, in alcoholism, and other addiction (carbohydrate) reward behaviors, it may also be involved in co-morbid antisocial personality disorder symptoms (especially in children and adults with attention deficit hyperactivity disorder (ADHD) or Tourette's Syndrome) and high novelty seeking.
Dopamine has been called the “anti-stress molecule” and/or the “pleasure molecule.” [Blum 1990]. When dopamine is released into the synapse, it stimulates a number of receptors (D1-D5), which results in increased feelings of well-being and stress reduction [Picetti 2013]. The mesocorticolimbic dopaminergic pathway plays an especially important role in mediating the reinforcement of natural rewards like food and sex, as well as unnatural rewards like drugs of abuse [Melis 2005]. Natural rewards include satisfaction of physiological drives (e.g., hunger and reproduction) and unnatural rewards are learned and involve satisfaction of acquired pleasures such as hedonic sensations derived from alcohol and other drugs, as well as from gambling and other risk-taking behaviors. [Blum 1996; Blum 2013; Blum 2014].
In discussing RDS, insensitivity and inefficiency in the reward system is specifically referred to. There may be a common neurocircuitry, neuroanatomy and neurobiology for multiple addictions and for a number of psychiatric disorders. [Bowirrat 2005]. Due to specific genetic antecedents and environmental influences (epigenetic) a deficiency of the D2 receptors may predispose individuals to a high risk for multiple addictive, impulsive, and compulsive behaviors. It is well known that alcohol and other drugs of abuse, as well as most positive reinforces (i.e., sex, food, gambling, aggressive thrills) cause activation and neuronal release of brain dopamine and involvement of the Na+/K+-ATPase. Dopamine release can decrease negative feelings and satisfy abnormal cravings for alcohol, cocaine, heroin and nicotine which among others are linked to low dopamine function. [Rothman 2007].
In doing association studies for which an investigator requires a representative control sample for a single RDS psychiatric diagnosis or for potential subsets of RDS, there are limitations that relate to controls poorly screened for multiple RDS behaviors and other related psychiatric disorders. Missing behaviors that are part of the RDS subset may be the reason for spurious results when genotyping for single subsets of RDS behaviors.
For example, an individual may not drink or use drugs but may have other RDS behaviors like overeating or intensive video gaming. In support of this notion, Blum et al. [Blum 2011] found a very strong association of the dopamine D2 receptor A1 allele (100%) in one Family (A). In addition, every individual in Family B also has at least one dopaminergic high risk allele (100%) (48% carried the DRD2 A1 allele]). Moreover, in family B only three adult individuals had no addictive behaviors. When this was compared with results in which 55 RDS subjects carried the DRD2 A1 allele at 78.2% with the results of Noble 2003 in which 597 severe alcoholics at (49.3%) carried the A1 allele, there was a significant difference between these two groups (χ2=16.9, p<0.001). This demonstrated that the A1 allele prevalence increases with multiple RDS behaviors.